| 1. |
- Strosberg, Jonathan, et al.
(författare)
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Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate : an analysis of the NETTER-1 study
- 2020
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 47:10, s. 2372-2382
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with Lu-177-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the Lu-177-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions Lu-177-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. : NCT01578239, EudraCT: 2011-005049-11
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| 2. |
- Case, Laura K., et al.
(författare)
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Encoding of Touch Intensity But Not Pleasantness in Human Primary Somatosensory Cortex
- 2016
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Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 36:21, s. 5850-5860
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Tidskriftsartikel (refereegranskat)abstract
- Growing interest in affective touch has delineated a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, have cast doubt on the segregation of touch discrimination and affect, suggesting that S1 also encodes affective qualities. We used functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to examine the role of S1 in processing touch intensity and pleasantness. Twenty-six healthy human adults rated brushing on the hand during fMRI. Intensity ratings significantly predicted activation in S1, whereas pleasantness ratings predicted activation only in the anterior cingulate cortex. Nineteen subjects also received inhibitory rTMS over right hemisphere S1 and the vertex (control). After S1 rTMS, but not after vertex rTMS, sensory discrimination was reduced and subjects with reduced sensory discrimination rated touch as more intense. In contrast, rTMS did not alter ratings of touch pleasantness. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1.
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| 3. |
- Case, Laura K., et al.
(författare)
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Inhibitory rTMS of secondary somatosensory cortex reduces intensity but not pleasantness of gentle touch
- 2017
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Ingår i: Neuroscience Letters. - : ELSEVIER IRELAND LTD. - 0304-3940 .- 1872-7972. ; 653, s. 84-91
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Tidskriftsartikel (refereegranskat)abstract
- Research suggests that the discriminative and affective aspects of touch are processed differently in the brain. Primary somatosensory cortex is strongly implicated in touch discrimination, whereas insular and prefronal regions have been associated with pleasantness aspects of touch. However, the role of secondary somatosensory cortex (S2) is less clear. In the current study we used inhibitory repetitive transcranial magnetic stimulation (rTMS) to temporarily deactivate S2 and probe its role in touch perception. Nineteen healthy adults received two sessions of 1-Hz rTMS on separate days, one targeting right S2 and the other targeting the vertex (control). Before and after rTMS, subjects rated the intensity and pleasantness of slow and fast gentle brushing of the hand and performed a 2-point tactile discrimination task, followed by fMRI during additional brushing. rTMS to S2 (but not vertex) decreased intensity ratings of fast brushing, without altering touch pleasantness or spatial discrimination. MRI showed a reduced response to brushing in S2 (but not in S1 or insula) after S2 rTMS. Together, our results show that reducing touch evoked activity in S2 decreases perceived touch intensity, suggesting a causal role of S2 in touch intensity perception. Published by Elsevier Ireland Ltd.
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| 4. |
- Liljencrantz, J., et al.
(författare)
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Pain and touch: Roles for c-tactile afferents in pain inhibition and tactile allodynia
- 2016
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Ingår i: Affective Touch and the Neurophysiology of CT Afferents. Olausson H., Wessberg J., Morrison I., McGlone F. (eds.). - New York : Springer. - 9781493964185 ; , s. 409-420
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In humans there is a positive correlation between the pleasantness perception of soft skin stroking and the firing rate of unmyelinated C-low-threshold mechanoreceptive afferents (often abbreviated C-LTMR in animals and C-tactile and CT afferents in humans). CT-targeted touch reduces heat pain in humans suggesting that activation of the CT system modulates pain perception. This finding is supported by animal work which has shown that C-LTMRs inhibit nociceptive signaling at the spinal cord level, release a protein (TAFA4) with analgesic effects, and have positively reinforcing and anxiolytic behavioral effects. However, under pathophysiological conditions, research in mice and humans instead suggests a role for CLTMRs and CTs in tactile allodynia. There is a divergence in results with some studies pointing to CLTMRs/CTs driving tactile allodynia, whereas others suggest a modulatory role. © 2016 Springer Science+Business Media New York.
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| 5. |
- Case, Laura K., et al.
(författare)
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Innocuous pressure sensation requires A-type afferents but not functional Rho Iota Epsilon Zeta Omicron 2 channels in humans
- 2021
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking A beta fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for A beta afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection. The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking A beta fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.
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| 6. |
- Case, Laura K., et al.
(författare)
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Pleasant Deep Pressure : Expanding the Social Touch Hypothesis
- 2021
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Ingår i: Neuroscience. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4522 .- 1873-7544. ; 464
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Tidskriftsartikel (refereegranskat)abstract
- Neuroscientific research on pleasant touch has focused on the C-tactile pathway for gentle stroking and has successfully explained how these sensory fibers transmit information about affective social touch to the brain and induce sensations of pleasantness. The C-tactile social/affective touch hypothesis even proposes that C-tactile fibers form a privileged pathway underlying social touch. However, deep pressure is a type of touch commonly considered pleasant and calming, occurring in hugs, cuddling, and massage. In this paper we introduce a paradigm for studying pleasant deep pressure and propose that it constitutes another important form of social touch. We describe development of the oscillating compression sleeve (OCS) as one approach to administering deep pressure and demonstrate that this touch is perceived as pleasant and calming. Further, we show that deep pressure can be imaged with functional magnetic resonance imaging (MRI) using the air-pressure driven OCS and that deep pressure activates brain regions highly similar to those that respond to C-tactile stroking, as well as regions not activated by stroking. We propose that deep pressure constitutes another social touch pathway of evolutionary importance signaling the close proximity of conspecifics. This article is part of a Special Issue entitled: The Neurobiology of Social and Affective Touch. (c) 2020 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/). research on pleasant touch has focused on the C-tactile pathway for gentle stroking and has successfully explained how these sensory fibers transmit information about affective social touch to the brain and induce sensations of pleasantness. The C-tactile social/affective touch hypothesis even proposes that C-tactile fibers form a privileged pathway underlying social touch. However, deep pressure is a type of touch commonly considered pleasant and calming, occurring in hugs, cuddling, and massage. In this paper we introduce a paradigm for studying pleasant deep pressure and propose that it constitutes another important form of social touch. We describe development of the oscillating compression sleeve (OCS) as one approach to administering deep pressure and demonstrate that this touch is perceived as pleasant and calming. Further, we show that deep pressure can be imaged with functional magnetic resonance imaging (MRI) using the air-pressuredriven OCS and that deep pressure activates brain regions highly similar to those that respond to C-tactile stroking, as well as regions not activated by stroking. We propose that deep pressure constitutes another social touch pathway of evolutionary importance signaling the close proximity of conspecifics. This article is part of a Special Issue entitled: The Neurobiology of Social and Affective Touch. (c) 2020 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
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| 7. |
- Case, Laura K, et al.
(författare)
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Touch Perception Altered by Chronic Pain and by Opioid Blockade.
- 2016
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Ingår i: eNeuro. - 2373-2822. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Touch plays a significant role in human social behavior and social communication, and its rewarding nature has been suggested to involve opioids. Opioid blockade in monkeys leads to increased solicitation and receipt of grooming, suggesting heightened enjoyment of touch. We sought to study the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor availability. The pleasantness of touch has been linked to the activation of C-tactile fibers, which respond maximally to slow gentle touch and correlate with ratings of pleasantness. We administered naloxone to patients and healthy controls to directly observe the consequences of µ-opioid blockade on the perceived pleasantness and intensity of touch. We found that at baseline chronic pain patients showed a blunted distinction between slow and fast brushing for both intensity and pleasantness, suggesting reduced C-tactile touch processing. In addition, we found a differential effect of opioid blockade on touch perception in healthy subjects and pain patients. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity. Further, in healthy individuals, naloxone-induced increase in touch pleasantness was associated with naloxone-induced decreased preference for slow touch, suggesting a possible effect of opioid levels on processing of C-tactile fiber input. These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients.
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| 8. |
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| 9. |
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| 10. |
- Olausson, Håkan, 1965, et al.
(författare)
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Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization.
- 2008
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Ingår i: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - : Springer Science and Business Media LLC. - 1432-1106. ; 184:1, s. 135-40
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Tidskriftsartikel (refereegranskat)abstract
- In addition to A-beta fibres the human hairy skin has unmyelinated (C) fibres responsive to light touch. Previous functional magnetic resonance imaging (fMRI) studies in a subject with a neuronopathy who specifically lacks A-beta afferents indicated that tactile C afferents (CT) activate insular cortex, whereas no response was seen in somatosensory areas 1 and 2. Psychophysical tests suggested that CT afferents give rise to an inconsistent perception of weak and pleasant touch. By examining two neuronopathy subjects as well as control subjects we have now demonstrated that CT stimulation can elicit a sympathetic skin response. Further, the neuronopathy subjects' ability to localize stimuli which activate CT afferents was very poor but above chance level. The findings support the interpretation that the CT system is well suited to underpin affective rather than discriminative functions of tactile sensations.
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